Structure of the yeast WD40 domain protein Cia1, a component acting late in iron-sulfur protein biogenesis

The WD40-repeat protein Cial is an essential, conserved member of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery in eukaryotes. Here, we report the crystal structure of Saccharomyces cerevisiae Cia1 to 1.7 angstrom resolution. The structure folds into a 0 propeller with seven blades pseudo symmetrically arranged around a central axis. Structure-based sequence alignment of Cial proteins shows that the WD40 propeller core elements are highly conserved. Site-directed mutagenesis of amino acid residues in loop regions with high solvent accessibility identified that the conserved top surface residue R127 performs a critical function: the R127 mutant cells grew slowly and were impaired in cytosolic Fe/S protein assembly. Human Ciao1, which reportedly interacts with the Wilms' tumor suppressor, WT1, is structurally similar to yeast Cial. We show that Ciao1 can functionally replace Cial and support cytosolic Fe/S protein biogenesis. Hence, our structural and biochemical studies indicate the conservation of Cia1 function in eukaryotes.